Whether induction of labor ahead in low-risk women improves pregnancy outcomes?: A retrospective cohort, observational study

The appropriate timing of delivery for pregnancies has always been a concern for medical staff, and the timing of elective labor induction at 41 weeks in low-risk pregnant women has always been controversial. We compared maternal and fetal outcomes between gestational age at 40 0/7 to 40 6/7 and 41 0/7 to 41 6/7 weeks. This retrospective cohort study was conducted at the obstetrics department of Jiangsu Province Hospital from January 1st to December 31st in 2020. Maternal medical records and neonatal delivery data were collected. One-way analysis of variance, Mann–Whitney U test, χ2 test, Fisher exact test and logistig regression analysis were performed. The study included 1569 pregnancies, with 1107 (70.6%) delivered at 40 0/7 to 40 6/7 weeks and 462 (29.4%) delivered at 41 0/7 to 41 6/7 weeks. Intrapartum cesarean section (8% vs 16%, P < .001), meconium-stained amniotic fluid (13% vs 19%, P = .004), episiotomy (41% vs 49%, P = .011), and macrosomia (13% vs 18%, P = .026) were significantly lower at 40 0/7 to 40 6/7 weeks. The premature rupture of membranes rate (22% vs 12%, P < .001), vaginal delivery rate of artificial rupture of membrane induction (83% vs 71%, P = .006) and balloon catheter combined with oxytocin induction (88% vs 79%, P = .049) were significantly higher at 40 0/7 to 40 6/7 weeks. Low-risk women who delivered at 40 0/7 to 40 6/7 weeks showed better outcomes in terms of the mother’s and baby’s health, such as decreased rates of intrapartum cesarean section, meconium-stained amniotic fluid, episiotomy, and macrosomia, compared with those who delivered at 41 0/7 to 41 6/7 weeks.


Introduction
The appropriate timing of delivery for pregnancies has always been a concern of medical staff. Fetal lung maturity gradually increases with gestational age, and premature delivery may lead to neonatal acidemia, whereas late delivery may increase maternal and neonatal risks. Neonates delivered at 36 to 38 weeks after confirmed fetal lung maturity are at higher risk of adverse outcomes than those delivered at 39 to 40 weeks. [1] Pulmonary maturity generally occurs after full-term birth (39 0/7-40 6/7 weeks). [2] Therefore, inducing pregnancy at 39 0/7 to 40 6/7 weeks may be proper from the angle of fetal lung maturity.
At present, elective labor induction is commonly performed after 41 weeks in low-risk women without labor onset. [3,4] However, with increases in gestational weeks, increases are observed in fetal weight, the probability of macrosomia, the rate of cephalopelvic disproportion, and the occurrence of shoulder dystocia, cesarean section, neonatal asphyxia and birth injury. [5][6][7][8] Thus, we sought to determine whether inducing low-risk pregnant women in advance at 40 weeks will lead to improved maternal and fetal outcomes. Therefore, the goal of this study was to compare maternal and fetal outcomes between gestational age at 40 0/7 to 40 6/7 and 41 0/7 to 41 6/7 weeks. Medicine

Study population
This retrospective cohort study assessed data from the obstetrics department of Jiangsu Province Hospital from January 1 st to December 31 st , 2020. These data included all maternal medical records and neonatal deliveries. The inclusion criteria were a low-risk singleton pregnancy delivered at 40 0/7 to 41 6/7 weeks of gestation at our hospital. Low-risk was defined as the absence of any condition that might be a maternal or fetal indication for delivery in a short time, such as any antepartum hypertensive disorder, cardiac disease or renal insufficiency. [9] Cases with electing cesarean delivery, vaginal birth after cesarean section and partial data loss were excluded. We divided pregnancies meeting the inclusion criteria into a full-term group (40 0/7-40 6/7 weeks) and a late-term group (41 0/7-41 6/7 weeks). [10] This study was approved by the Ethics Committee of Jiangsu Province Hospital [Ethics Committee 2020-SR-256].

Maternal complications.
The main variable exposed in our analysis was gestational age at delivery. The maternal complications were mainly episiotomy, instrumental delivery, intrapartum cesarean section (ICS), postpartum hemorrhage (PPH), shoulder dystocia, obstetric anal sphincter injury, meconium-stained amniotic fluid (MSAF), intrapartum cervical laceration, epidural analgesia, amniotic fluid embolism, and labor progression duration. An episiotomy performed at the time of crowning was defined as a surgical incision made to widen the vaginal opening for the delivery of the fetus. [11] Instrumental delivery was defined as vacuum extraction or forceps delivery. [12] In our hospital, it mainly referred to vacuum extraction. PPH was defined as blood loss in excess of 500 mL after vaginal delivery and in excess of 1000 mL after cesarean delivery in the first 24 hours after labor, and it was divided into mild PPH (estimated blood loss > 500 mL) and severe PPH (estimated blood loss > 1000 mL). [13] The total amount of blood loss was measured by weighing soaked materials and by use of the suction system and collector bags in the operating room. Shoulder dystocia was defined as the inability of the fetus to be delivered by traditional midwifery methods when the symphysis pubis obstructed the anterior descending of the shoulder or the posterior shoulder of the fetus was impacted on the maternal sacral promontory. [14] obstetric anal sphincter injury, including 3rd-and 4th-degree vaginal tears, damages the anal sphincter complex, and anorectal mucosa. [15] Intrapartum cervical laceration was defined as laceration with abnormal vaginal bleeding or requiring cervical suturing. [16] Amniotic fluid embolism was defined as the abnormal activation of proinflammatory mediator systems triggered by entrance into the maternal circulation of material from the fetal compartment. [17] The first stage of labor was defined as beginning from maternal perception of regular contractions to dilation. The second stage of labor was defined as the time from full dilation to delivery of the neonate. [3]

Neonatal complications
The neonatal complications were mainly macrosomia, neonatal intensive care unit (NICU) admission, 5-minute Apgar score ≤ 7, neonatal acidemia, subgaleal hemorrhage, glycopenia, neonatal jaundice, digestive syndrome, and clavicle fracture. Neonatal acidemia manifested as dyspnea, shallow and rapid breathing, moaning, and low pulse oxygen. We also diagnosed neonatal acidemia for umbilical artery pH < 7.1, chest X-ray abnormal and white blood cells > 20*10^9/L. [18] Hypoglycaemia was defined as a neonatal blood glucose < 2.5 mmol/L. [19] A pediatric professional doctor diagnosed neonatal jaundice requiring treatment through clinical examination and bilirubin levels due to the different peak serum bilirubin levels of neonates of different races.

Statistical analysis
All statistical analyzes were conducted using Excel and SPSS 26.0. Qualitative data were expressed as percentages (%), differences between groups were assessed by χ 2 test, and Fisher exact test was used to test significance. Normally distributed data were expressed as the mean ± standard deviation, and differences between groups were analyzed by 1-way analysis of variance. Nonnormally distributed data were expressed as the median (minimum, maximum), and differences between groups were tested using the Mann-Whitney U test. Logistic regression analysis was performed on the related factors that might be with statistical significance. Statistical significance was reached at P < .05.
Maternal characteristics in the study groups are compared in Table 1. A total of 1262 (approximately 80%) were nulliparous, and 73 (<5%) were assisted reproductive pregnancies. Approximately 60% of women had complications, including anemia, hypothyroidism, diabetes, and other unusual complications. Statistical significance was not observed in the cases of anemia or hypothyroidism between the 2 groups. The risk of premature rupture of membranes (PROM) in the full-term group was significantly higher than that in the late-term group (22% vs 12%, P < .001). The prevalence rate of gestational diabetes mellitus (GDM) in the full-term group was significantly higher than that in the late-term group (16% vs 8%, P < .001).
Different modes of labor are compared in Table 2. The spontaneous labor rate was significantly higher than that in the lateterm group (54% vs 20%, P < .001). The full-term group was lower than the late-term group in terms of the rate of induction of balloon catheter combined with oxytocin (BCCO) (9% vs 46%, P < .001), the rate of oxytocin induction (22% vs 27%, P = .012) and artificial rupture of membrane (AROM) induction (21% vs 31%, P < .001). The bishop score of parturient with BCCO induction was not statistically significant (P = .055). However, the late-term group had a higher final vaginal delivery rate of BCCO (88% vs 79%, P = .049) and AROM (83% vs 71%, P = .006). Significant differences were not observed in the vaginal delivery rate of oxytocin induction (80% vs 76%, P = .431).

Maternal outcomes
Maternal outcomes in the study groups are compared in Table 5. The successful vaginal delivery rate in the full-term group was significantly higher than that in the late-term group (90% vs 80%, P < .001), and the rate of episiotomy was also significantly decreased (41% vs 49%, P = .011). The risk of ICS in the full-term group was significantly lower than that in the late-term group (8% vs 16%, P < .001). Significant differences were not observed between the full-term and late-term groups in cephalopelvic disproportion (6% vs 10%, P = .073) or fetal distress (29% vs 39%, P = .133). The rate of MSAF in the late-term group was significantly higher than that in the full-term group  (19% vs 13%, P = .004). The epidural analgesia rate during labor in the full-term group was lower than that in the late-term group (76% vs 81%, P = .034). Significant differences were not observed in labor duration, postpartum hemorrhage, shoulder dystocia, or intrapartum cervical laceration rates between the 2 groups. After controlling and adjusting for the influence of confounding factors, compared with the late-term group, the full-term group had a higher risk of PROM (OR 3.25; 95% CI 2.18-4.84), GDM (OR 4.15; 95% CI 2.67-6.44) and vaginal delivery (OR 1.64; 95% CI 1.13-2.39) and a lower balloon catheter combined with oxytocin induction rate (OR 0.05, 95% CI 0.03-0.09), a lower oxytocin induction rate (OR 0.16; 95%CI 0.09-0.28). The maternal age, spontaneous labor rate, epidural analgesia rate, MSAF rate, NICU admission rate and AROM rate showed no difference between the 2 groups, as shown in Table 6.

Neonatal outcomes
Neonatal outcomes in the study groups are compared in Table 3. The average neonatal birth weight of the late-term group was higher than that of the full-term group (P < .001), and the macrosomia rate was also significantly higher than that   of the full-term group (18% vs 13%, P = .026). The main difference was in the range of 4000 to 4499 g (16% vs 12%, P = .042). Significant differences were not observed in the rates of NICU admission, 5-minute Apgar score ≤ 7, neonatal acidemia,   subgaleal haemorrhage, glycopenia, neonatal jaundice, swallowing syndrome or clavicle fracture between the 2 groups. Compared with the the late-term group, full-term group had the lower neonatal birth weight (OR 0.999, 95% CI 0.999-1.000), as shown in Table 6.

Discussions
At present, the timing of delivery is controversial, and many studies are exploring more suitable timings. Studies have shown that elective induction before 39 weeks increases the rate of NICU admission, prolongs the neonatal hospitalization time, results in a high readmission rate within 2 weeks after delivery, and increases emergency department visits. [20,21] A large multicenter RCT along with some retrospective studies showed that elective induction at 39 weeks reduced the cesarean section rate, pregnancy hypertension risk, perinatal infection, neonatal adverse perinatal outcomes (respiratory complications, NICU admission, perinatal death) and did not affect neonatal early literacy and numeracy ability. [9,22,23] Therefore, elective induction after 39 weeks in low-risk nulliparous women is recommended. However, there is little evidence for elective induction between 40 0/7 and 40 6/7 weeks. Nowadays, elective labor induction is commonly recommended after 41 weeks in low-risk women without labor onset. The reason for inducing until 41 weeks is to wait for the maturity of the cervix and to have higher chances of spontaneous labor and PROM. However, our study showed no difference in the bishop scores in the 2 groups and less opportunity for spontaneous labor and PROM after 41 weeks. If we need to induce these women by AROM or balloon catheter, then there is a higher rate for vaginal delivery at 40 0/7 to 40 6/7 weeks. Furthermore, we also found decreased ICS, meconium-stained amniotic fluid, episiotomy and macrosomia rates at 40 0/7 to 40 6/7 weeks. Studies have shown that the incidence of MSAF increases with gestational age, [24,25] which is consistent with our findings. Therefore, our study indicated that waiting until 41 weeks in low-risk women was not necessarily beneficial; however, our study is retrospective and needs to be further proven by prospective studies.
An international cohort study showed that after 39 weeks, the risk of PPH increased with gestational age. [26] Our results did not reflect this obvious difference, although preliminarily observations indicated that the rate of PPH in the late-term group was slightly greater than that in the full-term group (17% vs 14%, P = .226). If we increased the amount of data, statistical significance might be obtained. In our study, the prevalence rate of GDM in the full-term group was significantly higher than that in the late-term group. This might be because ACOG recommended that for women with GDM that was controlled with only diet and exercise, it was appropriate to control the gestation period within 40 6/7 weeks. [27] Those persisted beyond 41 weeks were due to lack of medical compliance. There was 1 case of amniotic fluid embolism in our study, which occurred during spontaneous vaginal delivery at 40 3/7 weeks. One hour after delivery, the patient experienced dyspnea, a sudden drop in blood pressure (86/42 mm Hg) and oxygen saturation (80%). After a series of rescue measures, such as open veins, oxygen inhalation, blood pressure boosting, and anti-allergic measures, the final prognosis was good.
Our study indicated that the macrosomia rate was higher at 41 0/7 to 41 6/7 weeks. No differences in adverse neonatal outcomes were noted in either group, which is consistent with a previous study. [21] Many studies have revealed the risks of macrosomia, such as shoulder dystocia, clavicle fractures, breathing problems, decreased 5-minute Apgar score, hypoglycemia, meconium aspiration, and more. [5][6][7][8] From this point of view, it is a wise choice to induce at 40 weeks to reduce the risk of macrosomia. However, our conclusion is not to overrule induction timing after 41 weeks. We found that PPH and NICU admission did not increase due to expectations; therefore, induction after 41 weeks cannot be considered inappropriate. For low-risk pregnant women without suspicious macrosomia, we can expect up to 41 weeks according to their willingness. Cavoretto's studies showed that longer labor duration [28] and higher meconium-stained amniotic fluid rate [29] could increase the risk of neonatal acidemia. In our study, there were no differences in labor duration and neonatal acidemia between the 2 groups, which was consistent with previous studies. However the MSAF rate decreased at at 40 0/7 to 40 6/7 weeks in our study, which seemed different from previous studies, and this might be due to the limited sample size.

Strengths and limitations
In China, elective labor induction is recommended after 41 weeks in low-risk women. Our study showed that induction of labor ahead might improve the pregnancy outcomes of these women. We believe our study may promote the development and research of relevant guidelines in China. Meanwhile, the limitations of our study should also be noted. This study was a single-center retrospective study, which was small in scale and some data records were easy to be missing, There are many factors affecting delivery, however the indicators included in this article could not cover all. Follow-up researches may need to increase the sample size and relevant observation indicators for further research to provide reference basis for clinical treatment plans.

Conclusions
In conclusion, deliveries at 40 0/7 to 40 6/7 weeks had better outcomes for low-risk mothers and their babies, such as decreased rates of ICS, meconium-stained amniotic fluid, episiotomy, and macrosomia, compared with deliveries at 41 0/7 to 41 6/7 weeks. From our results, we suppose that elective induction at 40 weeks of gestation might be superior to that at 41 weeks in terms of certain maternal and neonatal outcomes. However, in clinical practice, the appropriate timing of delivery should be discussed and choose a personalized delivery plan. Moreover, the conclusions remain to be further proven by prospective studies.